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Background: Tuberculosis (TB) is a public health problem worldwide. Characterizing its trends over time is a useful tool for decision-makers to assess the efficiency of TB control programs. We aimed to give an update on the current chronological trends of TB in Southern Tunisia from 1995 to 2016 and to estimate future trajectories of TB epidemic by 2030. Methods: We retrospectively collected data of all notified TB new cases by the Center of Tuberculosis Control between 1995 and 2016 in South of Tunisia. Joinpoint Regression Analysis was performed to analyze chronological trends and annual percentage changes (APC) were estimated. Results: In the past 22 years, a total of 2771 cases of TB were notified in Southern Tunisia. The annual incidence rate of TB was 13.91/100,000 population/year. There was a rise in all forms of TB incidence (APC = 1.63) and in extrapulmonary tuberculosis (EPTB) (APC = 2.04). The incidence of TB increased in children and adult females between 1995 and 2016 (APC = 4.48 and 2.37, respectively). The annual number of TB declined in urban districts between 2004 and 2016 (APC = -2.85). Lymph node TB cases increased (APC = 4.58), while annual number of urogenital TB decreased between 1995 and 2016 (APC = -3.38). Projected incidence rates would increase to 18.13 and 11.8/100,000 population in 2030 for global TB and EPTB, respectively. Conclusions: Our study highlighted a rise in all forms of TB and among high-risk groups, notably children, females and lymph node TB patients in the last two decades and up to the next one. [ABSTRACT FROM AUTHOR]